Zeitschriftenaufsatz
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2022
High Efficacy and Drug Synergy of HDAC6-Selective Inhibitor NN-429 in Natural Killer (NK)/T-Cell Lymphoma
Autor:in
Garcha, Harsimran K.; Nawar, Nabanita; Sorger, Helena; Erdogan, Fettah; Aung, Myint; Sedighi, Abootaleb; Manaswiyoungkul, Pimyupa; Seo, Hyuk-Soo; Schoenefeldt, Susann; Poloske, Daniel; Dhe-Paganon, Sirano; Neubauer, Heidi; Mustjoki, Satu; Herling, Marco; de Araujo, Elvin D.; Moriggl, Richard; Gunning, P.
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
NK/T-cell lymphoma (NKTCL) and gamma delta T-cell non-Hodgkin lymphomas (gamma delta T-NHL) are highly aggressive lymphomas that lack rationally designed therapies and rely on repurposed chemotherapeutics from other hematological cancers. Histone deacetylases (HDACs) have been targeted in a range of malignancies, including T-cell lymphomas. This study represents exploratory findings of HDAC6 inhibition in NKTCL and gamma delta T-NHL through a second-generation inhibitor NN-429. With nanomolar in vitro HDAC6 potency and high in vitro and in cellulo selectivity for HDAC6, NN-429 also exhibited long residence time and improved pharmacokinetic properties in contrast to older generation inhibitors. Following unique selective cytotoxicity towards gamma delta T-NHL and NKTCL, NN-429 demonstrated a synergistic relationship with the clinical agent etoposide and potential synergies with doxorubicin, cytarabine, and SNS-032 in these disease models, opening an avenue for combination treatment strategies.
Schlagwörter
NKTCL; HDAC6; synergy; combination treatment; small molecule inhibitor
Dokumententyp
Originalarbeit
CC Lizenz
CCBY
Open Access Type
Gold
10.3390/ph15111321
WoS ID
PubMed ID
Repository Phaidra